His main contribution was the germ plasm theory, according to which (in a multicellular organism) inheritance only takes place by means of the germ cells—the gametes such as egg cells and sperm cells. Other cells of the body—somatic cells—do not function as agents of heredity. The effect is one-way: germ cells produce somatic cells and are not affected by anything the somatic cells learn or therefore any ability the body acquires during its life. Genetic information cannot pass from soma to germ plasm and on to the next generation. This is referred to as the Weismann barrier.[2] This idea, if true, rules out the inheritance of acquired characteristics as proposed by Jean-Baptiste Lamarck.[3]

The idea of the Weismann barrier is central to the Modern evolutionary synthesis, though it is not expressed today in the same terms. In Weismann's opinion the largely random process of mutation, which must occur in the gametes (or stem cells that make them) is the only source of change for natural selection to work on. Weismann was one of the first biologists to deny soft inheritance entirely.[4] Weismann's ideas preceded the rediscovery of Gregor Mendel's work, and though Weismann was cagey about accepting Mendelism, younger workers soon made the connection.

Weismann is much admired today. Ernst Mayr judged him to be the most important evolutionary thinker between Darwin and the evolutionary synthesis around 1930-40, and was "one of the great biologists of all time".[5]